Disorders of Amino Acid Metabolism

Question 0

Tyrosinemia

Answer 0

• 5 types
• Type I: FAH deficiency
• metabolite accumulation&raquo_space; LIVER FAILURE with early failure of SYNTHETIC FUNCTION, hypophosphatemic rickets, FTT, parenthesis, seizures, paralysis
• restrict tyrosine and phenylalanine in diet, liver transplant, NTBC (block further upstream&raquo_space; build-up off less toxic metabolites
• Type II: tyrosine aminotransferase deficiency&raquo_space; tyrosine/phenolic acid accumulation
• OCULOCUTANEOUS: photophobia, corneal ulceration, crusted hyperkeratotic skin lesions (palms/soles), seizures, developmental delay

Question 1

PKU

Answer 1

• PAH Defect
  or biopterin deficiency: required for PAH function
• Can’t convert phenylalanine&raquo_space; tyrosine
• AR
• High phenylalanine&raquo_space; eczema, hypopigmentation, seizures, limb spasticity. MOUSY URINE ODOR, MR
• phenylalanine restricted diet, biopterin supplement

Question 2

MSUD

Answer 2

BCKD complex activity deficiency
accumulation of BCAA’s: leucine, isoleucine, valine
*leucine is NEUROTOXIC
Severe: lethargy, emesis, hypotonia, seizures- infancy
Intermediate: neuro decompensation during stress- child/adulthood
Chronic Progressive: gradual neuro dz (szrs, developmental delay)
*ammonia, lactate, bicarb often normal

Question 3

Homocystinuria

Answer 3

cystathionine beta-synthase deficiency
AR
homocysteine can’t&raquo_space; cystathionine
requires cofactor pyridoxine
Sx: MR, eye lens dislocation, MARFANOID BODY HABITUS, osteoporosis, acute vascular THROMBOSIS (50% by 30yo if untx)
Tx: 50% respond to pyridoxine (B6); limit METHIONINE in diet, extra cystine in diet, betaine (donates methyl to convert homocysteine to methionine instead of cystathionine)

Question 4

NKH: non-ketotic hyperglycinemia

Answer 4

glycine cleavage defect
Classic: lethargy, apnea, hypotonia, seizures in NB
EEG: BURST SUPPRESSION pattern
If survive&raquo_space; spastic CP
Late Onset: neurologic sx
Diagnosis: CSF : plasma glycine ratio > 0.08
no ketosis, acidosis
Tx: NaBenzoate, DM - reduce seizures, improve arousal
NO depakote - raises CSF glycine levels

Question 5

Alkaptonuria

Answer 5

homogentisate 1,2-dioxygenase deficiency
Hyperpigmentation: dark sclerae, ear cartilage, cerumen, urine
Arthritis in adults
Heart dz&raquo_space; MI